鸟苷酸环化酶参与血红素氧化酶1对抗心肌缺血/再灌注损伤的作用  

Involvement of GC in Effect of Heme Oxygenase-1 on Cardioprotection from Ischemia/reperfusion Induced injury

作　　者：汪洋[1] 徐和靖[2] 王万铁[1] 陈莹莹[3] 沈岳良[3] 杜友爱[2] 

机构地区：[1]温州医学院病理生理学教研室,浙江温州325035 [2]温州医学院生理教研室,浙江温州325035 [3]浙江大学医学院生理教研室

出　　处：《中国微循环》2006年第5期322-325,共4页Journal of Chinese Microcirculation

基　　金：温州市科技局科研基金(Y2005A025)

摘　　要：目的研究血红素氧化酶1(HO-1)在对抗心肌缺血/再灌注损伤中的作用,并探讨鸟苷酸环化酶(GC)是否参与其作用机制。方法采用离体大鼠心脏Langendorff灌流模型,观察心功能和酶学等指标。结果(1)HO-1的诱导剂高铁血红素可明显抑制缺血/再灌注心脏左室舒张末压(LV-EDP)增高,左室舒张压(LVDP)和最大左室收缩、舒张速率(±dP/dtmax)的下降;减少复氧期乳酸脱氢酶(LDH)释放,缩小心肌梗死面积(P<0.01)。(2)HO-1的抑制剂可加重缺血/再灌注心脏LVDP和±dP/dtmax下降,LDH释放和梗死面积明显高于单纯缺血/再灌注组(P<0.05)。(3)GC的抑制剂亚甲蓝可部分取消高铁血红素降低缺血/再灌注心脏LVEDP,增加LVDP和±dP/dtmax的作用,使LDH的释放和梗死面积明显增加(P<0.05)。结论诱导HO-1增加可保护缺血/再灌注心肌,其作用可能通过激动鸟苷酸环化酶途径来完成。Objective To investigate the role of HO-1 in protection of rat hearts from ischemia/reperfusion induced injury and its underlying mechanism. Methods Cardiac contractility, lactate dehydrogenase （LDH） and infarction area were analyzed by Langendorff method in isolated rat hearts. Results After intraperitoneal injection of HO-1 inducer heroin, CO concentration in rat blood enhanced（P〈0.01 vs control group）. Pretreatment of hemin prevented the increase in LVEDP and decrease in LVDP, ±dp/dtmax during the anoxia and reoxygenation period in hearts. Heme had no effect on changes of coronary flow, but it really inhibited the release of LDH from ischemia/reperfusion hearts. Heine also reduced the infarction area in anoxia heart after 2h reoxygenation（P〈0.01）. CO concentration in rat blood reduced after intraperitoneal injection of HO-1 inhibitor ZnPP（P〈0.01 vs control group）. ZnPP aggrevated the decrease in LVDP and ±dp/dtmax. Compared with ischemia/reperfusion heart, pretreatment of ZnPP enhanced the LDH release and enlarged the in- farction area（P〈0.05）. GC inhibitor methylene blue partly abolished the protective effect of heme on LVEDP, LVDP and ±dp/dtmax Pretreatment of methylene blue could also cancel the inhibition of LDH release and reduction of infarction area caused by heme（P〈0.05）. Conclusion HO-1 inducer heine could protect heart from ischemia/reperfusion induced injury. The cardiac protection of HO/CO might be through GC pathway.

关 键 词：心脏 缺血/再灌注 血红素氧化酶-1 鸟苷酸环化酶 

分 类 号：Q554.6[生物学—生物化学] Q554